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Biomedical subjects

N Conte

Publications and source records attributed to N Conte.

At least 19 recordsLinked to original sources

Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men.

This study was undertaken with the aim of investigating the cytogenetic constitution of normal as well as abnormal spermatozoa and immature germ cells found in semen of normal men and infertile patients. A specific protocol of double in-situ hybridization for chromosomes 1 and 17 based on colorimetric detection of the hybridization signals (ISH) and brightfield microscopy analysis of cellular morphology was applied. Also the influence of paternal age on sperm aneuploidy was investigated. We found that, at least in the age range analysed (28-54 years) and for semen of good quality (total normal motile counts above 10 x 10(6)) (n = 17), paternal age has no influence on baseline rates of sperm aneuploidy. However, with decreasing semen quality (total normal motile sperm counts below 5 x 10(6)) (n = 6) significantly higher rates of sperm aneuploidy for autosomes 1 and 17 were scored (0.8 versus 1.43%) (P < 0.001). Regardless of the type of semen analysed, a number of morphologically abnormal spermatozoa were found to be hyperhaploid or diploid in a high percentage of cases (20 and 10% respectively). The same was found for immature germ cells (aneuploidy rate of 18%). We conclude that in infertile men with poor quality semen a direct relationship may exist between the impairment of the spermatogenesis process (as reflected by an increased production of morphologically and cytogenetically abnormal germ cells) and rates of baseline aneuploidy occurring in normal spermatozoa. Infertile couples undergoing assisted reproduction treatment need to be counselled about the risk of using spermatozoa which may carry higher rates of non-disjunction for different chromosomes. While sperm hyper- or hypohaploidy for some chromosomes (X,Y) implies counselling couples about the risk of abnormal phenotype in their offspring, most autosomal sperm aneuploidies probably translate only into lower rates of embryo fertilization and survival.

Adult

Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations.

The effects of octreotide on biochemical markers of bone turnover were evaluated in patients with active acromegaly. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before and after 4 months of treatment in 27 patients (short-term treatment) and after 12 and 24 months of treatment in 15 patients (long-term treatment). In the short-term, octreotide significantly decreased the levels of serum GH, IGF-I, calcium, osteocalcin, carboxyterminal propeptide of type I collagen and alkaline phosphatase plus urinary excretion of calcium. Short-term treatment significantly increased serum parathormone levels (before treatment 30.1 +/- 9.57 and at 4 months 46.1 +/- 24.98 ng/L, p < 0.001) and urinary excretion of phosphate; urinary excretion of hydroxyproline was unchanged. The same results were observed during long-term treatment, except that there was no significant difference of serum calcium and alkaline phosphatase levels before and after treatment. Parathormone concentrations were still higher at 24 months compared with those prior to treatment (before treatment 31.9 +/- 9.74 and at 24 months 44.9 +/- 21.18 ng/L, p < 0.05). The changes of most bone markers during octreotide therapy can be explained by the decrease of serum GH and IGF-I concentrations. On the other hand, the rise of parathormone concentrations suggests that octreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the octreotide could contribute to this secondary hyperparathyroidism. The clinical consequences of these alterations of bone metabolism need to be further clarified.

Acromegaly

Comparison of gonosomal aneuploidy in spermatozoa of normal fertile men and those with severe male factor detected by in-situ hybridization.

The purpose of the study was to analyse the frequency of sex-chromosome numerical abnormalities in human spermatozoa of infertile men by using a standardized experimental protocol of double target in-situ hybridization (ISH). The experiments were performed on decondensed sperm heads from 15 infertile patients (six cases of unexplained infertility and nine cases of severe oligoasthenoteratozoospermia). Three men of proven fertility were used as controls. The probes employed recognized the centromeric regions of human X chromosome and the long arm of the Y chromosome. In a smaller number of cases, additional experiments of double ISH were performed using centromeric probes for chromosomes 1 and 17. Signal detection was based on protocols of enzymatic cytochemical reactions. A total of 24,508, 24,679 and 42,285 cells were scored in the control, unexplained infertility and severe male factor groups of patients respectively. In all the patients in the ISH efficiency result was approximately 98%. In controls, unexplained infertility and severe male factor patients, the frequency of morphologically normal sperm cells carrying an abnormal chromosome constitution (XX or YY or XY or > 2 sex chromosomes signals) was 0.86, 0.75 and 1.35% respectively. The value of this last group of patients (severe male factor) was significantly higher than in the other two groups of patients (P < 0.008). The same findings were made using the autosomic probes. Our preliminary data support the possibility of an increased risk from paternal origin sex chromosome aneuploidies in children born after intracytoplasmic sperm injection (ICSI). Further investigations of the cytogenetic constitution of spermatozoa from severe male factor patients is warranted.

Aneuploidy

[Acute hyperparathyroidism associated with follicular carcinoma in the thyroid: possible role of juvenile cervical irradiation. Description of a case].

Acute onset of primary hyperparathyroidism is uncommon; neuropsychiatric signs are prominent clinical features in acute hypercalcemia and they can subside after normalization of serum calcium. Radiation therapy is a well-known risk factor for non medullary thyroid cancer, but it induces also parathyroid tumors. Data from the literature show that patients previously treated with neck radiation have an increased risk of primary hyperparathyroidism. Furthermore concomitant thyroid cancer is more frequent in radiation-induced hyperparathyroidism than in sporadic primary hyperparathyroidism. The case of a 63-year-old female patient who at the age of 14 had been irradiated to the neck for goiter and at the age of 50 had been repeatedly hospitalized for psychosis is presented. She was admitted to the hospital for suspected recurrence of psychosis, but clinical findings and urgent biochemical data showed on the contrary that she had a severe hypercalcemic crisis. Serum parathormone concentrations, neck echography and 99mTc-Sestamibi scintigraphy suggested hyperfunction of the right lower parathyroid gland; therefore the patient was operated on. Pathological examination disclosed a parathyroid adenoma but also two foci of follicular cancer in the right thyroid lobe with a metastasis to a lymph node were observed. Neuropsychiatric signs disappeared after normalization of calcemia and 6 months after operation the patient is free from psychiatric symptoms, despite she had stopped neurolectic drugs. It is underlined that patients who had received neck irradiation must be carefully observed because they are at increased risk of primary hyperparathyroidism and concurrent thyroid cancer.

Acute Disease

Increased serum levels of carboxyterminal propeptide of type 1 collagen (PICP) in hyperthyroidism.

Type 1 collagen is the major organic constituent of the bone: its synthesis is reflected by the serum levels of type 1 procollagen C-terminal propeptide (PICP), which is therefore considered an index of osteoblastic activity. Serum PICP along with other serum and urinary markers of bone metabolism were measured in 16 untreated premenopausal females affected by Graves' disease and also in 7 of them after attainment of euthyroidism by methimazole treatment. Before treatment PICP was higher than sex and age-matched controls (324.19 +/- 101.74 vs. 131.44 +/- 26.25 micrograms/l, p < 0.001). Osteocalcin, alkaline phosphatase, serum calcium and urinary excretions of calcium and hydroxyproline were significantly increased with respect to controls, whereas parathormone was lower. Treatment induced a significant decrease of PICP, as well as calcemia, calciuria and hydroxyprolinuria compared to pretreatment values, while osteocalcin and alkaline phosphatase did not significantly differ. Non parametric correlation analysis showed positive correlation of free T3 and PICP (rs = 0.73, p < 0.005), osteocalcin and alkaline phosphatase; PICP was also significantly correlated with osteocalcin and alkaline phosphatase. Our data suggest that hyperthyroidism due to Graves' disease causes an increase of serum concentrations of PICP, which decrease after attainment of euthyroidism. The differences between PICP and BGP as markers of bone synthesis need to be further clarified.

Alkaline Phosphatase

[Serum levels of the tartrate-resistant isoenzyme, acid phosphatase, for the evaluation of bone remodeling in hyperthyroidism].

Tartrate-resistant acid phosphatase (TRAP) is one of the acid phosphatase isoenzymes. It is secreted by osteoclasts so it has been proposed as a marker of bone resorption. Bone turnover is high in hyperthyroidism due to an increase in both bone resorption and formation. The aim of the study was to measure serum TRAP as well as other markers of bone metabolism in 20 fertile age females affected by Graves-disease; 11 patients were also studied after euthyroid state was attained by means of a 6 month course of methimazole treatment. TRAP was measured with the colorimetric method using p-nitrophenylphosphate as substrate. Free thyroid hormones, TSH, serum calcium (corrected for albumin concentration), phosphate, osteocalcin, alkaline phosphatase, parathormone intact molecule, and urinary excretions of calcium, phosphate and hydroxyproline were measured, too. Twenty-eight healthy fertile women made up the control group. Untreated patients had a significant increase of TRAP, osteocalcin, serum calcium, alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A significant fall in all these parameters but alkaline phosphatase was disclosed comparing patients before and after treatment, nevertheless only urinary calcium became not significantly different from the controls. TRAP showed a significant correlation with free T3 levels but not with hydroxyproline excretions. This survey on fertile age women with Graves' disease shows a significant increase in serum concentration of TRAP, which decreases, but doesn't get normalization, when euthyroidism is attained by a six month course of methimazole therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase

Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma.

Parameters of bone turnover were measured in 20 premenopausal women affected by autonomous thyroid adenoma: 7 patients were suffering from overt hyperthyroidism with raised values of free thyroid hormones; 13 were clinically euthyroid and had normal values of free thyroid hormones. In all cases serum TSH concentrations were below the lower normal limit of our laboratory (< 0.4 mU/l). Eleven healthy premenopausal women were studied as a control group. Patients with overt hyperthyroidism disclosed a significant enhancement of both bone resorption (increased serum calcium and urinary excretion of hydroxyproline) and bone formation (increased serum levels of osteocalcin and alkaline phosphatase) when compared both to controls and to patients with subclinical hyperthyroidism. No significant alterations of bone metabolism parameters were found in patients with subclinical hyperthyroidism in comparison with controls. Therefore, in premenopausal women affected by autonomous thyroid adenoma the bone turnover appeared to be significantly increased when the serum values of free thyroid hormones were raised in the group of patients with overt hyperthyroidism.

Adenoma

Increased serum beta 2-microglobulin concentrations in hyperthyroid states.

Serum beta 2-microglobulin concentrations were determined in 21 untreated hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular adenoma) and in 20 healthy controls. All subjects had normal serum creatinine concentrations and urine analysis. Both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls. Beta 2-microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls. No difference was found in the thyroid hormone and beta 2-microglobulin concentrations between both sets of patients. The beta 2-microglobulin and thyroid hormone concentrations were not correlated. These data show that hyperthyroidism is another cause of increased beta 2-microglobulin production along with viral infections, immunologically mediated diseases, and malignant neoplasms. The increased serum beta 2-microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate, even if autoimmunity might contribute to its overproduction.

Adenoma

Clodronate treatment increases serum osteocalcin in normocalcemic osteolytic bone metastases.

28 consecutive patients with multiple osteolytic bone metastases due to various types of cancer were treated with 300 mg/day of sodium clodronate given intravenously as a 3-hour infusion, 16 patients were treated for 10 days and 12 for 20 days. Our findings showed that clodronate administration causes an increase in serum osteocalcin (sBGP) in the group of patients treated for 20 days (p less than 0.05), a reduction in serum Ca in both groups of patients (p less than 0.01), an increase in serum alkaline phosphatase (p less than 0.05 and p less than 0.01), a reduction in urinary Ca (p less than 0.01) and a reduction in uOHP (p less than 0.05). The raise in sBGP may be attributed to the reduction of sCa and to the consequent secondary hyperparathyroidism. The increase in sBGP can be considered as the expression of osteoblasts stimulation following an adequate period of therapy with sodium clodronate.

Adult

Serum bone GLA-protein in hypercalcemia of primary hyperparathyroidism and malignancy.

Serum bone GLA-protein, a modern and sensitive marker of bone turnover, was measured in 15 patients with primary hyperparathyroidism, 18 patients with hypercalcemia of malignancy, 41 patients with bone metastasis without hypercalcemia, and 29 healthy subjects. Serum bone GLA-protein was increased in primary hyperparathyroidism (17.6 +/- 3.9 ng/ml) and normal in hypercalcemia of malignancy (5.2 +/- 2.8 ng/ml; p less than 0.001 vs hyperparathyroidism) and in normocalcemic patients with bone metastases. In primary hyperparathyroidism parathyroid hormone correlated positively with urinary calcium excretion (p less than 0.05) and with urinary hydroxyproline excretion (p less than 0.001). The sensitivity of serum bone GLA-protein measurements in differentiating between primary hyperparathyroidism and hypercalcemia of malignancy was 91% and the specificity 84%. Thus this marker appears to be a useful tool for the differential diagnosis of hypercalcemias.

Adult

HLA antigens and haplotypes associated with idiopathic haemochromatosis in Veneto: peculiar association with HLA-A3,B35.

HLA-A and HLA-B antigens were determined in 16 unrelated subjects orginating from Veneto affected by idiopathic haemochromatosis (IH). HLA-A3 was found in 13/16 patients vs. 300/1,348 controls (p less than 0.00005). Prevalences of A3,B35 haplotype were 0.4375 in patients vs. 0.0816 in controls (p less than 0.0005). Linkage disequilibrium analysis proved the existence of a positive third-order linkage disequilibrium among IH, HLA-A3 and HLA-B35 alleles. Our data confirm the close association of IH and HLA-A3 and prove the peculiar association of the disease with A3,B35 haplotype in north-eastern regions of Italy. The positive third-order linkage disequilibrium suggests a remote event (mutation, recombination or immigration) as origin for IH and A3,B35 association.

Alleles

Apparently nonfunctioning metastases of parathyroid carcinoma.

A 41-year-old woman was operated on for severe hyperparathyroid syndrome. At surgery a parathyroid tumor with the histopathologic pattern of carcinoma was found. After surgery serum calcium settled within normal limits (10.5 mg/dl, N.V. 8.5-10.8), whereas parathormone and calcitonin reached progressively high levels, respectively 400 ng/dl (N.V. up to 250) and 500 pg/ml (N.V. up to 100 ng/ml). Serum ultrafiltration analysis for parathormone and calcitonin showed many peaks of immunoreactivity with high molecular weight of both hormones. One year after surgery, metastases developed in the lymph nodes of the neck and the mediastinal, pleural and pancreatic regions. After death for tumor wasting, immunohistochemical study of the tumoral tissue with the peroxidase-antiperoxidase technique showed a relatively high density of calcitonin-containing cells. The findings in this case suggest that: several cells in this parathyroid cancer could secrete both parathormone and calcitonin; the hormonal secretion was impaired as suggested by the high molecular weight of both hormones found at gel-filtration analysis; the macromolecular profile of parathormone could explain the apparent function of the parathyroid cancer.

Adult

The endogenous secretion rate of human calcitonin in normal conditions.

This paper presents a study on secretion rate for calcitonin in normal healthy subjects, evaluated by an indirect method. A specific radioimmunoassay for monomeric calcitonin was used and the obtained results are lower than those reported by Kanis in 1982. In normal healthy subjects the secretion rate for calcitonin is 1.4 MRC U/day, i.e. ten times less than the value calculated by Kanis. These results will be able to clarify the role of calcitonin and its effects in normal conditions and in several osteoarticular and metabolic bone diseases.

Adolescent

Hypercalcemia in malignancies: treatment with dichloromethylene diphosphonate (Cl2MDP).

Eleven hypercalcemic patients affected by various kinds of cancer were treated with dichloromethylene diphosphonate (Cl2MDP), 400 mg diluted in 500 ml of saline solution, i.v., during 3 h. Drug administration normalized plasma calcium levels in all treated patients, within 72 h for patients with lung cancer; within a longer period for other kinds of cancer. Moreover, Cl2MDP also reduced calciuria in treated patients. The use of the drug was not followed by side effects and was also well tolerated in patients with kidney insufficiency.

Adult

[Radioimmunological assay of alpha-fetoprotein in maternal serum and intrauterine fetal growth retardation].

Maternal plasma alpha-fetoprotein (AFP) was measured in fifteen women during first-mid-third-trimester of pregnancy. In three of these pregnacies by means ultrasound was relevable a condition of intrauterine growth retardation (IUGR). AFP was assayed by a double-antibody radioimmunoassay and values were compared with the median value of the normal range for the particular week of pregnancy. Plasma AFP levels were significantly higher in one subject with IUGR than in other patients.

Female